p27Kip1 is one of cyclin-dependent kinase inhibitors (CDK Inhibitors) that are a factor negatively regulating cell cycle progression. Clinical studies have revealed that the accelerated degradation of p27Kip1 decreases the expression amount of p27Kip1 in highly malignant cancer cells. Moreover, clinical studies suggest that the decrease in the expression amount of p27Kip1 closely relates to the progression, recurrence and metastasis of cancer and the decrease of survival ratio of patients with cancer.
p27Kip1 is mainly decomposed by ubiquitin-proteasome system to decrease in the amount of expression. More specifically, if threonine 187 of p27Kip1 is phosphorylated, p27Kip1 is isolated from a cyclin-CDK complex to specifically bind to F-box protein (Skp2) of a ubiquitin ligase comprising a SCF (Skp1/Cullin1/F-box) complex. Whereas, a ubiquitin conjugating enzyme (E2) binds to the ubiquitin ligase complex through Rbx1 in the complex, and p27Kip1 binding to Skp2 is ubiquitinated through the enzyme. By the repetition of the ubiquitination reaction, the polyubiquitinated p27Kip1 is recognized by a proteasome to be decomposed.
Thus the degradation mechanism of p27Kip1 has been explained molecular-biologically, but an effective p27Kip1 degradation inhibitor is still not known.
Incidentally, WO2005/012269 (Patent Document 1) discloses a compound represented by following formula as a physiologically active inhibitor of LPA acting as an intercellular messenger.

This document also discloses that the compound is useful as a treating or preventing agent for a cell proliferative disease, which is one of diseases in which a LPA receptor participates. The document, however, is silent on the relationship between the compound and an intracellular protein.